Open Label, Non-randomized Extension Trial to Assess Long Term Safety and Efficacy of Arimoclomol in Subjects With Amyotropic Lateral Sclerosis Who Have Completed the ORARIALS-01 Trial
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 120
- 试验地点
- 23
- 主要终点
- Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1)
研究概览
简要总结
A multicenter, non-randomized, open label trial, to assess long term safety and efficacy of Arimoclomol in subjects with Amyotrophic Lateral Sclerosis (ALS) who have completed the ORARIALS-01 trial.
详细描述
The planned duration of the open-label trial was 152 weeks, but the trial was terminated early as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints. Therefore, the actual mean duration of open-label treatment was approximately 28 weeks (range approximately 2 to 71 weeks).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject is able to comprehend and is willing to provide written informed consent and is capable and willing to comply with trial procedures, or in the circumstance that the subject is incompetent, informed consent/assent is provided in accordance with local regulation and/or procedures
- •Subject has completed the ORARIALS-01 trial (i.e., met one of the surrogate survival endpoints of tracheostomy or PAV or has completed the 76 weeks randomized treatment period)
- •Subject completed ORARIALS-01 while on treatment, where on treatment is defined as having taken the last dose of IMP within 2 weeks of the End of Trial visit (whether at week 76 or prior)
排除标准
- •Known or suspected allergy or intolerance to the IMP (Arimoclomol or constituents)
- •Exposure to any other investigational treatment, advanced therapy medicinal product or use of any other prohibited concomitant medications
- •Women who are lactating or pregnant, or men or women unwilling to use a highly effective method of birth control if not surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy, or hysterectomy for women; vasectomy for men) for female participants until 4 weeks after last dose and for male participants until 3 months after last dose. Pre-menopausal women must have a negative pregnancy test prior to dosing with trial medication.
- •Any of the following medically significant conditions:
- •Clinically significant renal or hepatic disease OR clinical laboratory assessment (results ≥ 3 times the upper limit of normal [ULN] for aspartate aminotransferase and/or alanine aminotransferase, bilirubin ≥ 2 times the ULN, or creatinine ≥ 1.5 times the ULN).
- •Any new condition or worsening of existing condition which, in the opinion of the investigator, would put the subject at undue risk.
- •Any serious adverse event or moderate/severe adverse event from the ORARIALS-01 trial which is ongoing at the time of transitioning to ORARIALS-02 and assessed as probably related to IMP
研究组 & 干预措施
Arimoclomol
248 mg arimoclomol base (equivalent to 400 mg arimoclomol citrate) 3 times daily
干预措施: Arimoclomol (Drug)
结局指标
主要结局
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1)
时间窗: Week 76
Standard clinical chemistry parameters. Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase.
Mean and Change From Baseline in Vital Signs - Blood Pressure
时间窗: Week 76
Standard vital signs. Systolic and diastolic blood pressure.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2)
时间窗: Week 76
Standard hematology parameters. Percentage of leukocytes were determined for basophils, eosinophils, lymphocytes, monocytes, and neutrophils
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematocrit
时间窗: Week 76
Standard hematology parameter.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Albumin and Protein
时间窗: Week 76
Standard clinical chemistry parameters.
Mean and Change From Baseline in Vital Signs - Temperature
时间窗: Week 76
Standard vital signs measurement.
Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period
时间窗: From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks
The C-SSRS is a detailed questionnaire assessing both suicidal behavior and suicidal ideation through a series of simple, plain-language questions administered as an interview by a qualified investigator or delegate.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period
时间窗: From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks
Adverse event (AE) data were collected throughout the trial until early termination. The average duration of exposure was 198.7 days (approximately 28 weeks; standard deviation 99.57 days; minimum 16 days, maximum 494 days). 58 participants (48.3%) were exposed less than 6 months; 55 participants (45.8%) were exposed 6 to less than 12 months; 7 participants (5.8%) were exposed 12 to less than 18 months. No participant was treated for 76 weeks. Participants with on-treatment TEAEs are reported. An on-treatment TEAE is any TEAE in the on-treatment period defined as the time from first dose of IMP until 14 days since the last preceding administration of IMP (either before a temporary IMP interruption with duration \>14 days or the last dose at the end of trial). A participant may have several on-treatment periods separated by interruption intervals.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Erythrocytes
时间窗: Week 76
Standard hematology parameter.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Cystatin C
时间窗: Week 76
Standard clinical chemistry parameter.
Mean and Change From Baseline in Vital Signs - Respiratory Rate
时间窗: Week 76
Standard vital signs measurement.
Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period
时间窗: From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks
Clinical safety laboratory data and vital signs were collected throughout the trial until early termination. The average duration of exposure was 198.7 days (approximately 28 weeks; standard deviation 99.57 days; minimum 16 days, maximum 494 days). 58 participants (48.3%) were exposed less than 6 months; 55 participants (45.8%) were exposed 6 to less than 12 months; 7 participants (5.8%) were exposed 12 to less than 18 months. No patient was treated for 76 weeks.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3)
时间窗: Week 76
Standard clinical chemistry parameters. Bilirubin, Creatinine, Direct Bilirubin, and Indirect Bilirubin.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1)
时间窗: Week 76
Standard hematology parameters. White blood cell differential count for basophils, eosinophils, leukocytes, lymphocytes, monocytes, and neutrophils, and platelet count.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hemoglobin
时间窗: Week 76
Standard hematology parameter.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2)
时间窗: Week 76
Standard clinical chemistry parameters. Calcium, Calcium Corrected, Cholesterol, Glucose, HDL Cholesterol, LDL Cholesterol, Potassium, Sodium, Triglycerides, and Urea Nitrogen.
Mean and Change From Baseline in Vital Signs - Pulse Rate
时间窗: Week 76
Standard vital signs measurement.
次要结局
- Change in ALS Functional Rating Scale - Revised (ALSFRS-R) From Baseline to Week 76(Week 76)
- Change in Percentage (%) Predicted Slow Vital Capacity (SVC) From Baseline to Week 76 (for Subjects Who Did Not Meet the Survival Endpoint in the ORARIALS-01 Trial)(76 weeks)